文摘
Behavioral evidence suggests that the organoselenium compound p,p¡ä-methoxyl-diphenyl diselenide [(MeOPhSe)2] ameliorates memory and learning performance in rodents. Here, we investigated the molecular mechanism of (MeOPhSe)2 neuroprotection in cortical neurons exposed to amyloid-¦Â (A¦Â) peptide as well as in A¦Â-infused mice. For this purpose, primary cultures of rat cortical neurons were pre-incubated with 10 ¦ÌM of (MeOPhSe)2 or vehicle, followed by exposure to 25 ¦ÌM A¦Â fragment 25-35 or vehicle. Furthermore, the therapeutic effect of (MeOPhSe)2 (5 mg/kg, oral route, daily for 5 days) on memory deficits was evaluated in mice exposed to A¦Â fragment 25-35 (3 nmol/3 ¦Ìl/per site, intracerebroventricular infusion). The results demonstrate that (MeOPhSe)2 prevented A¦Â-induced cell death in vitro, associated with inhibition of caspase-3 and -9 activities, poly (ADP-ribose) polymerase (PARP) cleavage and c-Jun N-terminal kinase (JNK) activation. Further, (MeOPhSe)2 rescued A¦Â-induced memory impairment in mice. In conclusion, (MeOPhSe)2 is neuroprotective in vitro and in vivo, suggesting that this organoselenium compound offers a potential treatment option for Alzheimer¡¯s disease.
